The project is a direct extension of project 1. The present project will evaluate in the brains of elderly depressed subjects with and without vascular deficits the cellular pathology of cortical prefrontal areas that have been found to be involved in depression. The specific aim of the project is to estimate quantitatively the changes in the morphology and distribution of neurons and glial cells in dorsolateral area 9, lateral orbitofrontal area 47 and medial prefrontal area 12 in postmortem brains from matched depressive subjects with vascular deficits, depressives without vascular disease, and elderly controls. To achieve this objective we will measure morphological features of neurons, glia and blood vessels using Cresyl Violet (Nissl staining) for the study of the general cellular cytoarchitecture and immunohistochemical methods modified for labeling of cytoskeletal and calcium-binding proteins in neurons and glial fibrillary acid protein in glial cells in celloidin-embedded human brain sections. In addition, similar morphometric parameters will be measured in the homological regions of the prefrontal cortex in the VMAT2 and NET knockout mouse representing an animal model of depression. The measurements will be carried out using a computer-assisted stereological counting method. To understand whether specific pathology is associated with depression in old age with or without vascular diseases is important, because it will contribute to establish specific therapeutic basis for a differential treatment of depression in the elderly with vascular disorders. Alternatively, it may turn out that idiopathic and vascular depression share many pathological characteristics, which will suggest that a common treatment for both would be possible.